Abstract
Within arterial bifurcations or branching points, oscillatory shear stress (OSS) induces oxidative stress mainly via the reduced nicotinamide adenine dinucleodtide phosphate (NADPH) oxidase system. It is unknown whether 17β-estradiol (E2) can regulate OSS-mediated low-density lipoprotein (LDL) modifications. Bovine aortic endothelial cells were pretreated with E2 at 5 nmol/L, followed by exposure to OSS (0 ± 3.0 dynes/cm2 s and 60 cycles/min) in a flow system. E2 decreased OSS-mediated NADPH oxidase mRNA expression, and E2-mediated {radical dot}NO production was mitigated by the NO synthase inhibitor N(G)-nitro-l-argenine methyl ester. The rates of O2 -{radical dot} production in response to OSS increased steadily as determined by superoxide-dismutase-inhibited ferricytochrome c reduction; whereas, pretreatment with E2 decreased OSS-mediated O2 -{radical dot} production (n = 4, p < 0.05). In the presence of native LDL (50 μg/mL), E2 also significantly reversed OSS-mediated LDL oxidation as determined by high-performance liquid chromatography. In the presence of O2 -{radical dot} donor, xanthine oxidase (XO), E2 further reversed XO-induced LDL lipid peroxidation (n = 3, p < 0.001). Mass spectra acquired in the m/z 400-1800 range, revealed XO-mediated LDL protein nitration involving tyrosine 2535 in the α-2 domains, whereas pretreatment with E2 reversed nitration, as supported by the changes in nitrotyrosine intensities. Thus, E2 plays an indirect antioxidative role. In addition to upregulation of endothelial {radical dot}NO synthase and downregulation of Nox4 expression, E2 influences LDL modifications via lipid peroxidation and protein nitration.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 568-578 |
| Number of pages | 11 |
| Journal | Free Radical Biology and Medicine |
| Volume | 41 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 15 2006 |
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Keywords
- 17β-Estradiol
- LDL lipid oxidation and nitration
- NADPH oxidase
- Nitric oxide
- Shear stress
- Superoxide anion
ASJC Scopus subject areas
- Medicine(all)
- Toxicology
- Clinical Biochemistry
Cite this
17β-Estradiol reverses shear-stress-mediated low density lipoprotein modifications. / Hwang, Juliana; Rouhanizadeh, Mahsa; Hamilton, Ryan T.; Lin, Tiantian C.; Eiserich, Jason P.; Hodis, Howard N.; Hsiai, Tzung K.
In: Free Radical Biology and Medicine, Vol. 41, No. 4, 15.08.2006, p. 568-578.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 17β-Estradiol reverses shear-stress-mediated low density lipoprotein modifications
AU - Hwang, Juliana
AU - Rouhanizadeh, Mahsa
AU - Hamilton, Ryan T.
AU - Lin, Tiantian C.
AU - Eiserich, Jason P.
AU - Hodis, Howard N.
AU - Hsiai, Tzung K.
PY - 2006/8/15
Y1 - 2006/8/15
N2 - Within arterial bifurcations or branching points, oscillatory shear stress (OSS) induces oxidative stress mainly via the reduced nicotinamide adenine dinucleodtide phosphate (NADPH) oxidase system. It is unknown whether 17β-estradiol (E2) can regulate OSS-mediated low-density lipoprotein (LDL) modifications. Bovine aortic endothelial cells were pretreated with E2 at 5 nmol/L, followed by exposure to OSS (0 ± 3.0 dynes/cm2 s and 60 cycles/min) in a flow system. E2 decreased OSS-mediated NADPH oxidase mRNA expression, and E2-mediated {radical dot}NO production was mitigated by the NO synthase inhibitor N(G)-nitro-l-argenine methyl ester. The rates of O2 -{radical dot} production in response to OSS increased steadily as determined by superoxide-dismutase-inhibited ferricytochrome c reduction; whereas, pretreatment with E2 decreased OSS-mediated O2 -{radical dot} production (n = 4, p < 0.05). In the presence of native LDL (50 μg/mL), E2 also significantly reversed OSS-mediated LDL oxidation as determined by high-performance liquid chromatography. In the presence of O2 -{radical dot} donor, xanthine oxidase (XO), E2 further reversed XO-induced LDL lipid peroxidation (n = 3, p < 0.001). Mass spectra acquired in the m/z 400-1800 range, revealed XO-mediated LDL protein nitration involving tyrosine 2535 in the α-2 domains, whereas pretreatment with E2 reversed nitration, as supported by the changes in nitrotyrosine intensities. Thus, E2 plays an indirect antioxidative role. In addition to upregulation of endothelial {radical dot}NO synthase and downregulation of Nox4 expression, E2 influences LDL modifications via lipid peroxidation and protein nitration.
AB - Within arterial bifurcations or branching points, oscillatory shear stress (OSS) induces oxidative stress mainly via the reduced nicotinamide adenine dinucleodtide phosphate (NADPH) oxidase system. It is unknown whether 17β-estradiol (E2) can regulate OSS-mediated low-density lipoprotein (LDL) modifications. Bovine aortic endothelial cells were pretreated with E2 at 5 nmol/L, followed by exposure to OSS (0 ± 3.0 dynes/cm2 s and 60 cycles/min) in a flow system. E2 decreased OSS-mediated NADPH oxidase mRNA expression, and E2-mediated {radical dot}NO production was mitigated by the NO synthase inhibitor N(G)-nitro-l-argenine methyl ester. The rates of O2 -{radical dot} production in response to OSS increased steadily as determined by superoxide-dismutase-inhibited ferricytochrome c reduction; whereas, pretreatment with E2 decreased OSS-mediated O2 -{radical dot} production (n = 4, p < 0.05). In the presence of native LDL (50 μg/mL), E2 also significantly reversed OSS-mediated LDL oxidation as determined by high-performance liquid chromatography. In the presence of O2 -{radical dot} donor, xanthine oxidase (XO), E2 further reversed XO-induced LDL lipid peroxidation (n = 3, p < 0.001). Mass spectra acquired in the m/z 400-1800 range, revealed XO-mediated LDL protein nitration involving tyrosine 2535 in the α-2 domains, whereas pretreatment with E2 reversed nitration, as supported by the changes in nitrotyrosine intensities. Thus, E2 plays an indirect antioxidative role. In addition to upregulation of endothelial {radical dot}NO synthase and downregulation of Nox4 expression, E2 influences LDL modifications via lipid peroxidation and protein nitration.
KW - 17β-Estradiol
KW - LDL lipid oxidation and nitration
KW - NADPH oxidase
KW - Nitric oxide
KW - Shear stress
KW - Superoxide anion
UR - http://www.scopus.com/inward/record.url?scp=33746210016&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746210016&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2006.04.010
DO - 10.1016/j.freeradbiomed.2006.04.010
M3 - Article
VL - 41
SP - 568
EP - 578
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 4
ER -